APPLICANT'S ABSTRACT: Background and Objectives Schizophrenic have 3-4 fold higher prevalence rates of ethanol abuse disorders than the general population. Comorbid ethanol use/abuse has a significant negative impact on the course and treatment of schizophrenia. The existing literature about ethanol effects in schizophrenics is limited by its exclusive reliance on post-hoc reports of subjective drug effects; while ethanol's effects on positive and negative symptoms of schizophrenia remain unclear, ethanol may reduce anxiety, dysphoria and iatrogenic negative symptoms in schizophrenics. Our pilot data suggests that ethanol may reduce positive symptoms and increase negative symptoms in schizophrenics. In addition, ethanol appeared to have some dose and group-related differences. There are no pharmacological studies characterizing the effects of ethanol in schizophrenics. This proposal is the first prospective attempt to our knowledge, to study the acute dose-related behavioral, cognitive, and motor effects of ethanol in schizophrenics. This study is intended as a first in a series of studies exploring the problem of ethanol and schizophrenia. Research Plan and Methodology: Stable, neuroleptic-treated schizophrenics without previous ethanol abuse disorder will be compared to age, sex and education matched healthy controls. A comparison group of healthy controls is included because ethanol's mechanism of action suggests that it has unique effects in schizophrenics. Subjects will be studied under three conditions (placebo, low blood alcohol level - 0.002-0.004%, and high blood alcohol condition - 0.06-0.08%), in a double-blind, randomized, counterbalanced design. The primary outcome measures include: 1) 4 key positive and 3 key negative symptom subscales, of the Brief Psychiatric Rating Scale (BARS) 2) tests sensitive to frontal and temporal cortical function: Continuous Performance Test and the Hopkins Verbal Learning Test. Secondary outcome measures will include: 1) Biphasic Alcohol Effects Scale, 2) Visual Analog Scale for Mood States, 3) The simpson Angus Scale for Parkinsonism, 4) Barnes Akathisia scale, and 5) other cognitive tests. BARS data in schizophrenics will be analyzed using a repeated measures ANOVA with, within subjects factors for time for time and ethanol dose. Data from the biphasic Alcohol Effects Scale and cognitive tests will be initially analyzed using a repeated measures ANOVA with within subjects factors of ethanol dose and time, and a between subjects factors for diagnosis. For differences between patients and controls (cognitive test performance, blood alcohol levels, etc.,), relevant data will be added into the analysis as covariates. Post-hoc testing of peak changes from baseline will be conducted if there are significant time effects in the analysis using Dunnett's multiple t-tests. Results from this study will be used to guide the development of further, more comprehensive studies comparing alcohol abusing vs. Non-abusing schizophrenics and studying neurobiological correlates.